Endonasal transsphenoidal surgery is a minimally invasive procedure that involves grinding away sphenoidal bone in the nasal cavity to access and resect pituitary tumors. Each surgery incurs the risk of death resulting from injury to the carotid arteries located behind the sphenoidal bone on either side of the pituitary gland. The long-term objective of this project is to develop the imaging technology required for real-time photoacoustic visualization of blood vessels and bone to eliminate the risk of striking a carotid artery during surgery. The specific aims of the mentored phase are to: (1) image vessel-like targets embedded in phantoms surrounded by cranial bone to characterize system requirements; and (2) develop the mathematical framework for optimized, coherence-based photoacoustic signal detection and display. This phase will be pursued at Johns Hopkins University, a pioneering institution of transsphenoidal surgeries. The specific aims of the independent phase will build on the knowledge obtained during the mentored phase to design and assess a new class of coherence-based beamformers that overcome expected challenges with laser penetration, leading to the eventual building, testing, and validation of a dedicated prototype system. The methods used to achieve these aims will include integration of beamforming theory with commercially-available optical equipment and ultrasound machines to form customized photoacoustic imaging systems. The systems will be tested on tissue-mimicking phantoms and human head models that simulate surgeries, culminating with a pilot study on patients undergoing transsphenoidal surgeries. Quantitative metrics and observer studies are proposed to compare and assess image quality, while in vivo and ex vivo visualization of vessels and vessel-like targets will be correlated with endoscopic and magnetic resonance images. Although the system will initially be developed for transsphenoidal surgeries, it will be useful in any minimally- invasive surgery that requires visualization of hidden blood vessels. In addition, the proposed coherence-based photoacoustic beamformers have broader implications for improving image quality and overcoming current depth penetration limits in multiple photoacoustic applications. My expert advisory team will consist of mentors and collaborators in interventional photoacoustics, optics, medical image analysis, neurosurgery, and the design of surgical systems. I will combine my experience in developing and implementing the first short-lag spatial coherence (SLSC) beamformer and my background in ultrasound physics and mechanical engineering with proposed training and career development in optics. Successful completion of the proposed plan promises to unlock new possibilities for clinical applications of photoacoustic imaging.